What I Learned From the Study of Sex Differences in Pulmonary Hypertension: How Following the Data and the Kindness of Strangers Helped Me Overcome Self‐Doubt and Imposter Syndrome

“Why is there more variation in the females? Could it be due to their estrous cycle?” This was the question my co-mentor, Dr. Irina Petrache, posed when I shared the first data I generated as a first-year research fellow. It was 2007, and was in the lab of cardiothoracic surgeon Dr. Dan Meldrum at Indiana University. Dan studied sex differences in cardiac ischemia–reperfusion injury in the left ventricle. With his model of isolated rat pulmonary artery rings, I joined to explore pulmonary vascular disease. Drawing on Dan's focus on sex biases in the left ventricle, I compared hypoxic pulmonary vasoconstriction in arteries from male and female rats. After gathering sufficient data, I was disappointed: no statistical difference. Before Dan's lab meeting, I consulted Irina. Her insight inspired a plan: a well-designed PowerPoint presentation, a literature review on the effects of the estrous cycle, and experiments on rats of both sexes, along with plans to assess the effects of the estrous cycle on hypoxic vasoconstriction in pulmonary arteries from female rats. Dan agreed to the study, which found that hypoxic pulmonary vasoconstriction varied with the cycle, attenuating at high estrogen levels. This yielded my first “first-author paper” in the American Journal of Physiology [1]. I was thrilled that I—a working-class German country boy with no lab experience and who had never held a pipette in his hand—could publish a research paper in this august journal. This study on sex differences in pulmonary hypertension (PH) stemmed from experiences 2 years prior. As a second-year internal medicine resident on an elective in Kenya, I saw young women, not men, with severe right heart failure from indoor stove smoke-induced emphysema. Their EKGs showed extreme right ventricle remodeling. Researching sex differences felt like a natural progression of that prior observation. As I worked on my research in Dan's lab, I decided to attend a PH workshop at the National Institutes of Health in 2007. It was an inspiring meeting but imposter syndrome hit hard then. Would anyone value my work? Or did it make sense? But there, I met Dr. Steve Kawut, whose poster showed better right ventricle adaptation in female PH patients [2]. This validated my research's relevance. Emailing him postmeeting, he became a mentor and friend, aiding my career generously. I also met a larger-than-life figure named Dr. Norbert Voelkel who after a proper introduction (“Hi, I'm Tim, and you worked with my mentor on an AHA document on right heart failure”) told me that other scientists found sex differences in left ventricle remodeling and encouraged me to keep doing research in this field. I also met Dr. Mark Gladwin who after a proper introduction (“Hi, I'm Tim, and you worked with my mentor on an AHA document on right heart failure”) was nothing short of generous and encouraged me to keep working in PH. I also started building my own scientific peer group and community. At ATS 2009 in San Diego, Dr. John Newman discussed estrogens in PH in a talk. This was the first time I heard someone discuss this at a national meeting. I introduced myself to talk to him about this, and he said that I should speak to Dr. Anna Hemnes, as she was studying androgen signaling in right heart failure. Irina introduced me to Anna at the same ATS, and we have been close collaborators and friends since then. Over the next 1–2 years, Drs. Corey Ventetuolo, Vinicio de Jesus Perez, Eric Austin, and many other peers became good friends and collaborators as well. After those initial uplifting encounters, challenges mounted. One lab (well-established in PH) published findings that were opposite of mine and flooded the field [3]. I worried that despite my previously published data I could be on the wrong track. Another lab whose data aligned with mine published their data before I was able to publish mine [4]. I panicked at conferences where these groups presented their data. I thought my career was finished. But mentor Irina rescued me: “Just follow the data and do your best; it'll be fine.” She was spot-on. I soon published a widely cited paper in a high-impact journal [5]. However, more setbacks emerged: Due to citizenship reasons, I could not apply for NIH career development awards; VA funding failed. My first NIH R01 took four attempts to get funded. Throughout that time, I wanted to quit on multiple occasions. A few years prior, in 2007, Dr. Rubin Tuder called studying sex hormones “a mess.” He was right. This area prompted deep reflection, heightening my temptation to quit, yet I tried to strengthen my resolve. What saved me were my mentors and professional network. The experiences that my mentors and friends shared, the community we created, and my own desire to make a difference in the field are what kept me going. Ultimately, I was able to establish a career as an independent scientist and soon was able to become a mentor to a new generation of scientists. I persevered. I was lucky to meet amazing mentors and role models early in my career. Mentors like Irina, Dan, Steve, Norbert, Mark Gladwin, John, and Mark Nicolls (who provided invaluable feedback along the way), and friends like Anna, Corey, Vinicio, and Eric were crucial to my career development. Their support and wisdom enabled questioning, persistence, and mentoring new scientists [6, 7]. Dedicated to my parents, who taught me to show up and work hard, and to my mentors, who taught me to be curious and brave. The vignettes were authored solely by Dr. Tim Lahm. The author thanks Dr. Ghazwan Butrous for stimulating scientific discussion and Dr. Darlene Kim for critical proofreading and editing. Financial support was provided by the NIH 5R01HL144727, VA Merit Review Award 7I01 BX002042, NIH 1P01 HL158507, and the Borstein Family Foundation. The author has nothing to report. The author declares no conflicts of interest.